The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

IL1B  -  interleukin 1, beta

Homo sapiens

Synonyms: Catabolin, IL-1, IL-1 beta, IL-1B, IL1-BETA, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of IL1B

  • CONCLUSIONS: This study provides evidence supporting the independent protective role of cagA-positive H. pylori status and IL1B and ILRN allele polymorphisms against GERD [1].
  • OBJECTIVE: To study the role of the interleukin-1 beta gene (IL1B) and the IL-1 receptor antagonist gene (IL1RN) in relation to the occurrence of radiographic osteoarthritis (ROA) in the hip, knee, and hand and disc degeneration of the spine [2].
  • The most consistent results are the increased gastric cancer risk associated with IL1B and NAT1 variants, which may account for up to 48% of attributable risk of gastric cancer [3].
  • Polymorphisms of the IL1B gene have been associated with gastric atrophy and increased cancer risk, especially in Helicobacter pylori-infected subjects [4].
  • The aim of this study was to evaluate the relationship between IL1B and IL1 receptor antagonist gene polymorphisms and the risk of multifocal atrophic gastritis in African Americans and Caucasians [4].

Psychiatry related information on IL1B


High impact information on IL1B

  • In rheumatoid joint cell cultures that spontaneously produce IL-1, TNF alpha was the major dominant regulator of IL-1 [10].
  • Twenty weeks after the end of supplementation, the production of IL-1 beta, IL-1 alpha, and tumor necrosis factor had returned to the presupplement level [11].
  • VCAM-1 mRNA is present in endothelial cells at 2 hr after treatment with IL-1 or TNF-alpha and is maintained for at least 72 hr; leukocyte binding activity parallels mRNA induction [12].
  • TRAF6 is a signal transducer that activates IkappaB kinase (IKK) and Jun amino-terminal kinase (JNK) in response to pro-inflammatory mediators such as interleukin-1 (IL-1) and lipopolysaccharides (LPS) [13].
  • Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target [14].

Chemical compound and disease context of IL1B


Biological context of IL1B

  • In our transient transfection assays using human THP-1 monocytic cells, a chloramphenicol acetyltransferase (CAT) construct containing the IL1B promoter sequence between positions -131 and +12 showed an approximately 90-fold increase in activity following cotransfection of a Tax expression vector [20].
  • EMSAs using THP-1 cell nuclear extracts indicated that IL-1beta significantly induced Spi-1 binding to its target site within the IL1B promoter that was maximal at 1 h after stimulation, correlating with the kinetics of IL-1beta induction [21].
  • CONCLUSION: These data suggest that polymorphisms within the promoter region of the IL1B gene contribute to observed differences in LPS-induced IL-1 beta protein secretion [22].
  • Analysis of 3-marker sliding windows revealed significant and consistent associations with all of the haplotypes in the IL1A and IL1B loci in the Alberta cohort and with IL1B in the Newfoundland cohort, especially haplotypes rs1143634/rs1143630/rs3917356 and rs1143630/rs3917356/rs3917354 (P = 0.006-0.0001) [23].
  • Two polymorphisms within IL1B (3953C>T and -511C>T) and one within IL1RN (the variable-number tandem repeat [VNTR]) were analyzed and used in an association study of the occurrence of ROA [2].

Anatomical context of IL1B


Associations of IL1B with chemical compounds


Physical interactions of IL1B

  • Excess unlabeled IL-1 beta or IL-1ra blocked the binding of 125I-IL-1 beta to the IL-1RtII [32].
  • At least in the case of the IL1B promoter, repression did not seem to involve another factor whose activity is affected by the NSAIDs, NFkappaB as the IL1B promoter fragment used in our studies is not NFkappaB responsive and binds specifically to HSF1 [26].
  • Although human IL-1 alpha and IL-1 beta have similar affinities and cross-compete for binding to the human Type I IL-1R, the binding site residues are not identical in the two ligands [33].
  • Internalization at 37 degrees C demonstrated that only 19% of IL-1 beta was internalized and that binding with IL-1 alpha was entirely cell surface [34].
  • The IL-1R accessory protein (IL-1RAcP) plays a role in IL-1R signaling by forming a complex with IL-1RI bound to the IL-1 ligand [35].

Enzymatic interactions of IL1B


Regulatory relationships of IL1B


Other interactions of IL1B

  • However, this upregulation in homeostatic regulatory mechanisms is not sufficient as these are unable to neutralize all the TNF alpha and IL-1 produced [10].
  • Two distinct but distantly related complementary DNAs encoding proteins sharing human interleukin-1 (IL-1) activity (termed IL-1 alpha and IL-1 beta), were isolated from a macrophage cDNA library [45].
  • RESULTS--Mean serum IL-6 levels, but not IL-1 beta or tumor necrosis factor-alpha levels, correlated with organ failure (r = 0.79, P < .001) [46].
  • After this early wave, a second phase begins that is sustained and leads to an elevated production of IL-8 that appears to be due to the endogenous release of TNF and IL-1 beta [47].
  • IFN-gamma (but none of the other cytokines) inhibited TNF-alpha-induced proliferation (70 +/- 14% inhibition) without affecting the activity of IL-1 [48].

Analytical, diagnostic and therapeutic context of IL1B

  • In electrophoretic mobility shift assays (EMSA) using in vivo THP-1 nuclear extracts, Tax expression in THP-1 monocytic cells significantly increased binding of the two factors to their target IL1B promoter sequences [20].
  • IL1RN, IL1A and IL1B genotypes were determined using restriction-enzyme analysis [49].
  • STUDY DESIGN AND METHODS: This study was undertaken to investigate whether there is an association between the polymorphisms of IL1B -511C/T and +3953C/T, IL1RN intron 2 VNTR and TNFA-308G/A genes and the increase of cytokines during the storage of PLT concentrates produced by plasma-rich PLTS (PRP-PC) or apheresis PLTs [50].
  • Genotyping for the C/T transition at position -511 in the promoter region of IL1B, for the single base M235T polymorphism of Agt, and for the missense Glu298Asp variant of Nos3 was performed using PCR, an allele-specific oligonucleotide hybridization assay, and pyrosequencing, respectively [51].
  • Northern blot analysis demonstrated that steady-state IL-8 mRNA expression, by either TNF- or IL-1 beta-treated A549 cells, occurred in both a dose- and time-dependent fashion [52].


  1. IL1B and IL1RN polymorphic genes and Helicobacter pylori cagA strains decrease the risk of reflux esophagitis. Queiroz, D.M., Guerra, J.B., Rocha, G.A., Rocha, A.M., Santos, A., De Oliveira, A.G., Cabral, M.M., Nogueira, A.M., De Oliveira, C.A. Gastroenterology (2004) [Pubmed]
  2. Association of the interleukin-1 gene cluster with radiographic signs of osteoarthritis of the hip. Meulenbelt, I., Seymour, A.B., Nieuwland, M., Huizinga, T.W., van Duijn, C.M., Slagboom, P.E. Arthritis Rheum. (2004) [Pubmed]
  3. Genetic susceptibility and gastric cancer risk. González, C.A., Sala, N., Capellá, G. Int. J. Cancer (2002) [Pubmed]
  4. Association of interleukin-1beta gene polymorphisms with precancerous gastric lesions in African Americans and Caucasians. Zabaleta, J., Camargo, M.C., Piazuelo, M.B., Fontham, E., Schneider, B.G., Sicinschi, L.A., Ferrante, W., Balart, L., Correa, P., Ochoa, A.C. Am. J. Gastroenterol. (2006) [Pubmed]
  5. Association of IL-1 RN*2 allele and methionine synthase 2756 AA genotype with dementia severity of sporadic Alzheimer's disease. Bosco, P., Guéant-Rodríguez, R.M., Anello, G., Romano, A., Namour, B., Spada, R.S., Caraci, F., Tringali, G., Ferri, R., Guéant, J.L. J. Neurol. Neurosurg. Psychiatr. (2004) [Pubmed]
  6. Tumor necrosis factor-alpha: is there a continuum of liability between stress, anxiety states and anorexia nervosa? Holden, R.J., Pakula, I.S. Med. Hypotheses (1999) [Pubmed]
  7. Interactions between HIV-infected monocyte-derived macrophages and human brain microvascular endothelial cells result in increased expression of CC chemokines. Boven, L.A., Middel, J., Breij, E.C., Schotte, D., Verhoef, J., Soderland, C., Nottet, H.S. J. Neurovirol. (2000) [Pubmed]
  8. Differential effects of IL-1ra on sickness behavior and weight loss induced by IL-1 in rats. Bluthé, R.M., Beaudu, C., Kelley, K.W., Dantzer, R. Brain Res. (1995) [Pubmed]
  9. Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system: an evaluation of cytokines in cerebrospinal fluid. Gallo, P., Frei, K., Rordorf, C., Lazdins, J., Tavolato, B., Fontana, A. J. Neuroimmunol. (1989) [Pubmed]
  10. Role of cytokines in rheumatoid arthritis. Feldmann, M., Brennan, F.M., Maini, R.N. Annu. Rev. Immunol. (1996) [Pubmed]
  11. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. Endres, S., Ghorbani, R., Kelley, V.E., Georgilis, K., Lonnemann, G., van der Meer, J.W., Cannon, J.G., Rogers, T.S., Klempner, M.S., Weber, P.C. N. Engl. J. Med. (1989) [Pubmed]
  12. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Osborn, L., Hession, C., Tizard, R., Vassallo, C., Luhowskyj, S., Chi-Rosso, G., Lobb, R. Cell (1989) [Pubmed]
  13. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Wang, C., Deng, L., Hong, M., Akkaraju, G.R., Inoue , J., Chen, Z.J. Nature (2001) [Pubmed]
  14. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Thornberry, N.A., Bull, H.G., Calaycay, J.R., Chapman, K.T., Howard, A.D., Kostura, M.J., Miller, D.K., Molineaux, S.M., Weidner, J.R., Aunins, J. Nature (1992) [Pubmed]
  15. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Casey, L.C., Balk, R.A., Bone, R.C. Ann. Intern. Med. (1993) [Pubmed]
  16. Ebselen and cytokine-induced nitric oxide synthase expression in insulin-producing cells. de-Mello, M.A., Flodström, M., Eizirik, D.L. Biochem. Pharmacol. (1996) [Pubmed]
  17. Interleukin-1 beta stimulates cell proliferation in the intermediate lobe of the rat pituitary gland. Stepień, H., Zerek-Mełen, G., Mucha, S., Winczyk, K., Fryczak, J. J. Endocrinol. (1994) [Pubmed]
  18. Inflammatory mediators of the terminal dentition in adult and early onset periodontitis. Salvi, G.E., Brown, C.E., Fujihashi, K., Kiyono, H., Smith, F.W., Beck, J.D., Offenbacher, S. J. Periodont. Res. (1998) [Pubmed]
  19. Prostaglandin E2 and I2 regulate intercellular adhesion molecule-1 expression in interleukin-1 beta-stimulated human gingival fibroblasts. Iwasaki, K., Noguchi, K., Ishikawa, I. J. Periodont. Res. (1999) [Pubmed]
  20. Human T-cell leukemia virus type I Tax transactivates the promoter of human prointerleukin-1beta gene through association with two transcription factors, nuclear factor-interleukin-6 and Spi-1. Tsukada, J., Misago, M., Serino, Y., Ogawa, R., Murakami, S., Nakanishi, M., Tonai, S., Kominato, Y., Morimoto, I., Auron, P.E., Eto, S. Blood (1997) [Pubmed]
  21. Autocrine induction of the human pro-IL-1beta gene promoter by IL-1beta in monocytes. Toda, Y., Tsukada, J., Misago, M., Kominato, Y., Auron, P.E., Tanaka, Y. J. Immunol. (2002) [Pubmed]
  22. Correlation of polymorphic variation in the promoter region of the interleukin-1 beta gene with secretion of interleukin-1 beta protein. Hall, S.K., Perregaux, D.G., Gabel, C.A., Woodworth, T., Durham, L.K., Huizinga, T.W., Breedveld, F.C., Seymour, A.B. Arthritis Rheum. (2004) [Pubmed]
  23. Association of the IL1 gene cluster with susceptibility to ankylosing spondylitis: an analysis of three Canadian populations. Maksymowych, W.P., Rahman, P., Reeve, J.P., Gladman, D.D., Peddle, L., Inman, R.D. Arthritis Rheum. (2006) [Pubmed]
  24. T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region. Wang, Z.C., Yunis, E.J., De los Santos, M.J., Xiao, L., Anderson, D.J., Hill, J.A. Genes Immun. (2002) [Pubmed]
  25. The association between periodontal disease and joint destruction in rheumatoid arthritis extends the link between the HLA-DR shared epitope and severity of bone destruction. Marotte, H., Farge, P., Gaudin, P., Alexandre, C., Mougin, B., Miossec, P. Ann. Rheum. Dis. (2006) [Pubmed]
  26. Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes. Housby, J.N., Cahill, C.M., Chu, B., Prevelige, R., Bickford, K., Stevenson, M.A., Calderwood, S.K. Cytokine (1999) [Pubmed]
  27. Interleukin-1 receptor antagonist. Arend, W.P. Adv. Immunol. (1993) [Pubmed]
  28. Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. Genis, P., Jett, M., Bernton, E.W., Boyle, T., Gelbard, H.A., Dzenko, K., Keane, R.W., Resnick, L., Mizrachi, Y., Volsky, D.J. J. Exp. Med. (1992) [Pubmed]
  29. Proinflammatory cytokines found in amniotic fluid induce collagen remodeling, apoptosis, and biophysical weakening of cultured human fetal membranes. Kumar, D., Fung, W., Moore, R.M., Pandey, V., Fox, J., Stetzer, B., Mansour, J.M., Mercer, B.M., Redline, R.W., Moore, J.J. Biol. Reprod. (2006) [Pubmed]
  30. -511 C/T IL1B gene polymorphism is associated to resistance to bisphosphonates treatment in Paget disease of bone. Corral-Gudino, L., del Pino-Montes, J., García-Aparicio, J., Corral, E., Montilla, C.A., González-Sarmiento, R. Bone (2006) [Pubmed]
  31. Glucocorticoid inhibits the human pro-interleukin lbeta gene (ILIB) by decreasing DNA binding of transactivators to the signal-responsive enhancer. Waterman, W.R., Xu, L.L., Tetradis, S., Motyckova, G., Tsukada, J., Saito, K., Webb, A.C., Robinson, D.R., Auron, P.E. Mol. Immunol. (2006) [Pubmed]
  32. Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: I. IL-1 receptor antagonist inhibits IL-1-induced cytokine synthesis and blocks the binding of IL-1 to its type II receptor on human monocytes. Granowitz, E.V., Clark, B.D., Vannier, E., Callahan, M.V., Dinarello, C.A. Blood (1992) [Pubmed]
  33. Site-directed mutagenesis--molecular biology and rational drug design. Ju, G., Labriola-Tompkins, E., Varnell, T., Madison, V., Graves, B. Agents Actions Suppl. (1995) [Pubmed]
  34. Heterogeneity in interleukin (IL)-1 receptors expressed on human B cell lines. Differences in the molecular properties of IL-1 alpha and IL-1 beta binding sites. Benjamin, D., Wormsley, S., Dower, S.K. J. Biol. Chem. (1990) [Pubmed]
  35. Antibodies to domains II and III of the IL-1 receptor accessory protein inhibit IL-1 beta activity but not binding: regulation of IL-1 responses is via type I receptor, not the accessory protein. Yoon, D.Y., Dinarello, C.A. J. Immunol. (1998) [Pubmed]
  36. Interleukin-1 activates a novel protein kinase that phosphorylates the epidermal-growth-factor receptor peptide T669. Kracht, M., Shiroo, M., Marshall, C.J., Hsuan, J.J., Saklatvala, J. Biochem. J. (1994) [Pubmed]
  37. Negative regulation of toll-like receptor-mediated signaling by Tollip. Zhang, G., Ghosh, S. J. Biol. Chem. (2002) [Pubmed]
  38. Identification and characterization of CPP32/Mch2 homolog 1, a novel cysteine protease similar to CPP32. Lippke, J.A., Gu, Y., Sarnecki, C., Caron, P.R., Su, M.S. J. Biol. Chem. (1996) [Pubmed]
  39. Production, purification, and crystallization of human interleukin-1 beta converting enzyme derived from an Escherichia coli expression system. Malinowski, J.J., Grasberger, B.L., Trakshel, G., Huston, E.E., Helaszek, C.T., Smallwood, A.M., Ator, M.A., Banks, T.M., Brake, P.G., Ciccarelli, R.B. Protein Sci. (1995) [Pubmed]
  40. Assay for IkappaB kinases using an in vivo biotinylated IkappaB protein substrate. Wisniewski, D., LoGrasso, P., Calaycay, J., Marcy, A. Anal. Biochem. (1999) [Pubmed]
  41. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. Marui, N., Offermann, M.K., Swerlick, R., Kunsch, C., Rosen, C.A., Ahmad, M., Alexander, R.W., Medford, R.M. J. Clin. Invest. (1993) [Pubmed]
  42. Expression of interleukin 1-inducible genes and production of interleukin 1 by aging human fibroblasts. Kumar, S., Millis, A.J., Baglioni, C. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  43. Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist. Vannier, E., Miller, L.C., Dinarello, C.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  44. Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Hiscott, J., Marois, J., Garoufalis, J., D'Addario, M., Roulston, A., Kwan, I., Pepin, N., Lacoste, J., Nguyen, H., Bensi, G. Mol. Cell. Biol. (1993) [Pubmed]
  45. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. March, C.J., Mosley, B., Larsen, A., Cerretti, D.P., Braedt, G., Price, V., Gillis, S., Henney, C.S., Kronheim, S.R., Grabstein, K. Nature (1985) [Pubmed]
  46. Leukocyte activation in the peripheral blood of patients with cirrhosis of the liver and SIRS. Correlation with serum interleukin-6 levels and organ dysfunction. Rosenbloom, A.J., Pinsky, M.R., Bryant, J.L., Shin, A., Tran, T., Whiteside, T. JAMA (1995) [Pubmed]
  47. Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. Cassatella, M.A., Meda, L., Bonora, S., Ceska, M., Constantin, G. J. Exp. Med. (1993) [Pubmed]
  48. Cytokines in chronic inflammatory arthritis. V. Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on HLA-DR expression, proliferation, collagenase production, and granulocyte macrophage colony-stimulating factor production by rheumatoid arthritis synoviocytes. Alvaro-Gracia, J.M., Zvaifler, N.J., Firestein, G.S. J. Clin. Invest. (1990) [Pubmed]
  49. Functional correlates of the interleukin-1 receptor antagonist gene polymorphism in the colonic mucosa in ulcerative colitis. Carter, M.J., Jones, S., Camp, N.J., Cox, A., Mee, J., Warren, B., Duff, G.W., Lobo, A.J., di Giovine, F.S. Genes Immun. (2004) [Pubmed]
  50. Interleukin 1 beta and tumor necrosis factor levels in stored platelet concentrates and the association with gene polymorphisms. Addas-Carvalho, M., Origa, A.F., Saad, S.T. Transfusion (2004) [Pubmed]
  51. Polymorphisms of the angiotensinogen gene, the endothelial nitric oxide synthase gene, and the interleukin-1beta gene promoter in women with idiopathic recurrent miscarriage. Hefler, L.A., Tempfer, C.B., Bashford, M.T., Unfried, G., Zeillinger, R., Schneeberger, C., Koelbl, H., Nagele, F., Huber, J.C. Mol. Hum. Reprod. (2002) [Pubmed]
  52. Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. Standiford, T.J., Kunkel, S.L., Basha, M.A., Chensue, S.W., Lynch, J.P., Toews, G.B., Westwick, J., Strieter, R.M. J. Clin. Invest. (1990) [Pubmed]
WikiGenes - Universities